This is a joint proposal from an experimental nephrology group and a group working on extracellular matrix molecular biology to study the accumulation of the extracellular matrix (ECM) in diabetic kidney disease. Synthesis of ECM components will be studied in a glomerular organ culture system previously used by this group in establishing the central role of transforming growth factor-beta (TGF-Beta) in the deposition of ECM into nephritic glomeruli. Antibodies to ECM components associated with increased TGF-Beta activity, wound healing and complement activity will be used to characterize the specific features of the diabetic glomerular matrix in a rat diabetes model and in samples from patients. The expression of proteoglycans, various forms of ECM glycoproteins, with integrin-type receptors for ECM, and various forms of TGF-Beta will be evaluated with antibodies and molecular probes. If evidence for the involvement of TGF-Beta in the pathogenesis of diabetic kidney disease is obtained, suppression of the syndrome with specific antibodies and other substances capable of blocking TGF-Beta activity will be attempted. Alternative pathogenetic mechanisms for the matrix accumulation in diabetic kidney disease will also be considered. These studies will provide new molecular information on the structure of the diabetic glomerular ECM and may lead to understanding of the pathogenetic mechanisms of the ECM accumulation as well as point to ways of preventing it.